Control of protein synthesis and degradation will be investigated in the perfused rat heart. These controls appear to underlie regulation of cardiac size and to be involved in the mechanisms of cardiac atrophy and hypertrophy. The perfused rat heart is a suitable model for these studies since perfusate levels of hormones and substrates can be closely controlled and mechanical activity can be varied by changing left atrial filling pressure, afterload, cardiac output and heart rate. Protein synthesis appears to be regulated at the level of peptide-chain initiation by insulin and availability of fatty substrates and amino acids. Protein degradation accelerates during perfusion and appears to be controlled by these same factors. Interaction of control of protein turnover by hormonal and metabolic factors with control by mechanical activity of the heart will be investigated. Control of protein synthesis and degradation in hearts undergoing cardiac atrophy and hypertrophy are being studied during perfusion in vitro and in vivo following hypophysectomy and aortic-banding, respectively. The extent of methylation of heart proteins in vivo as well as factors which modify the rate of protein methylation in vitro are being investigated. BIBLIOGRAPHIC REFERENCES: Jefferson, L.S., D.E. Rannels, J.B. Li., R.L. Kao and H.E. Morgan. Diabetes, insulin, fatty acids and the control of protein turnover in heart and skeletal muscle. Symposium on Metabolic Regulation and Diabetes, in press (l976). Rannels, D.E., E.E. McKee and H.E. Morgan. Regulation of protein synthesis and degradation in heart and skeletal muscle. In: Biochemical Actions of Hormones, Vol. 4 (G. Litwack, ed.) in press (l976).